Paracoccidioidomycosis: advances and unmet needs 100 years after its initial description by Lutz

Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaUNIFESP, Depto. de MedicinaSciEL

Epidemiology of hematogenous infections due to Candida spp

Candida spp is associated to almost 80% of all nosocomial fungal infections and is considered a major cause of blood stream infections. Candida spp is the fourth most common cause of blood stream infections in the United States, where this agent is responsible for 8% of all invasive infections documented in this site. At the present, non-albicans species are related to at least 50% of all invasive infections due to Candida spp and they present differences in terms of clinical outcome as well as susceptibility to antifungal drugs. The crude mortality rate of candidemia is between 40 and 60% which makes this infection an important challenge for all clinicians from tertiary care hospitals of diverse different countries.O gênero Candida spp é responsável por cerca de 80% das infecções fúngicas no ambiente hospitalar e constitui causa relevante de infecções de corrente sanguínea. Nos Estados Unidos da América, Candida spp é a quarta causa mais comum de infecções de corrente sanguínea, respondendo por cerca de 8% dos casos das infecções documentadas neste sítio. Espécies não-albicans respondem hoje por ao menos 50% das infecções invasivas por Candida spp, apresentando peculiaridades de história natural e sensibilidade a antifúngicos. A mortalidade geral de fungemias por Candida spp é da ordem de 40 a 60%, tornado esta complicação infecciosa um grande desafio para os clínicos que trabalham em hospitais terciários em diferentes países.Universidade Federal de São Paulo (UNIFESP)Hospital do Servidor Público Estadual de São PauloUNIFESPSciEL

Candida auris: What Have We Learned About Its Mechanisms of Pathogenicity?

Candida auris has emerged globally as a multidrug-resistant (MDR) medical care-associated fungal pathogen. Recent reports have demonstrated that C. auris usually expresses fewer virulence factors than does Candida albicans. However, the tendency of C. auris transmission within and between healthcare facilities is unique among Candida spp. and is possibly promoted by virulence and pathogenicity factors that facilitate skin colonization and environmental persistence. To understand the ability of this yeast to cause disease, we herein discuss several virulence and pathogenicity aspects of C. auris

Specification of the PERFoRM architecture for the seamless production system reconfiguration

The world is assisting to the fourth industrial revolution, with several domains of science and technology being strongly developed and, specially, being integrated with each other, allowing to build evolvable complex systems. Data digitization, big-data analysis, distributed control, Industrial Internet of Things, Cyber-Physical Systems and self-organization, amongst others, are playing an important role in this journey. This paper considers the best practices from previous successful European projects addressing distributed control systems to develop an innovative architecture that can be industrially deployed. For this purpose, a particular design process has to be addressed in order to consider the requirements and functionalities from various use cases. To investigate the known practices, four use cases are enlighted in this paper, which cover a wide spectrum of the European industrial force, as well as industrial standards to support a smooth migration from traditional systems to the emergent distributed systems.info:eu-repo/semantics/publishedVersio

Systematic review and new insights into the molecular characterization of the Candida rugosa species complex

Recently, Candida rugosa was characterized as a species complex comprising four taxa: C rugosa sensu stricto, Candida pseudorugosa, Candida neorugosa and Candida mesorugosa. Although considered relatively rare, several clusters of candidemia due to C rugosa complex had been reported presenting mortality rates close to 70%. in this work we discuss the systematization, phenotyping and molecular methods based on internal transcribed spacer region (ITS) sequencing and proteomic analyses for species identification, as well as clinical aspects of the C rugosa complex. We performed a Bayesian phylogenetic analysis using 72 ITS sequences representative of C rugosa complex isolates and related species within the genus. Biochemical, morphological and MALDI-TOF MS analyses were processed with C rugosa complex type strains and related species isolates. We described that the phylogeny showed four distinct clades inferred with high posterior probabilities, corresponding to the four species within the C. rugosa complex, excluding C. pararugosa. Biochemical and morphological aspects distinguished only C rugosa sensu strict but were not sufficient to accurately identify species within the rest of the complex. Protein spectrum profiles differentiated all reference strains from different species analyzed. To our knowledge, we presented the first phylogenetic analysis using a large collection of ITS sequences as well as proteomic profiles generated from isolates of the C rugosa complex and related species that can enlighten systematics, diagnostics and clinical research fields. (C) 2013 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Disciplina Infectol, Lab Especial Micol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Infectol, Lab Especial Micol, BR-04039032 São Paulo, BrazilFAPESP: 2007/08575-1FAPESP: 2009/10155-6CAPES: PNPD 02640-09-0Web of Scienc

Current Knowledge of Trichosporon spp. and Trichosporonosis

Trichosporon spp. are basidiomycetous yeast-like fungi found widely in nature. Clinical isolates are generally related to superficial infections. However, this fungus has been recognized as an opportunistic agent of invasive infections, mostly in cancer patients and those exposed to invasive medical procedures. It is possible that the ability of Trichosporon strains to form biofilms on implanted devices, the presence of glucuronoxylomannan in their cell walls, and the ability to produce proteases and lipases are all factors likely related to the virulence of this genus and therefore may account for the progress of invasive trichosporonosis. Disseminated trichosporonosis has been increasingly reported worldwide and represents a challenge for both diagnosis and species identification. Phenotypic identification methods are useful for Trichosporon sp. screening, but only molecular methods, such as IGS region sequencing, allow the complete identification of Trichosporon isolates at the species level. Methods for the diagnosis of invasive trichosporonosis include PCR-based methods, Luminex xMAP technology, and, more recently, proteomics. Treating patients with trichosporonosis remains a challenge because of limited data on the in vitro and in vivo activities of antifungal drugs against clinically relevant species of the genus. Despite the mentioned limitations, the use of antifungal regimens containing triazoles appears to be the best therapeutic approach.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Lab Especial Micol, Disciplina Infectol, BR-04023062 São Paulo, BrazilUniv Fed Rio Grande do Norte, Lab Micol Med Mol, Dept Anal Clin Toxicol, BR-59072970 Natal, RN, BrazilUniversidade Federal de São Paulo, Lab Especial Micol, Disciplina Infectol, BR-04023062 São Paulo, BrazilFAPESP: 2005/02006-0FAPESP: 2005/04442-1FAPESP: 2007/08575-1CNPq: 308011/2010-4CAPES: PNPD 02640-09-0Web of Scienc

A global perspective of the changing epidemiology of invasive fungal disease and real-world experience with the use of isavuconazole.

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions

In Vitro Antifungal Susceptibility of Clinically Relevant Species Belonging to Aspergillus Section Flavi

The in vitro antifungal susceptibility of 77 isolates belonging to different clinically relevant species of Aspergillus section Flavi, including those of different phylogenetic clades of A. flavus, was tested for nine antifungal agents using a microdilution reference method (CLSI, M38-A2). Terbinafine and the echinocandins demonstrated lower MICs/MECs for all species evaluated, followed by posaconazole. Amphotericin B showed MICs >= 2 mu g/ml for 38 (49.4%) of the 77 isolates tested.Spanish Ministerio de Educacion y CienciaCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Med, Special Mycol Lab LEMI, São Paulo, BrazilUniv Rovira & Virgili, Sch Med, IISPV, Mycol Unit, E-43201 Reus, SpainUniversidade Federal de São Paulo, Dept Med, Special Mycol Lab LEMI, São Paulo, BrazilSpanish Ministerio de Educacion y Ciencia: CGL 2009-08698/BOSCAPES: SWE 4150-08-2CAPES: 2312/2011CNPq: GM/GD 142051/2007-1FAPESP: 2012/01134-8Web of Scienc

Epidemiology of fungal infections in liver transplant recipients: a six-year study of a large Brazilian liver transplantation centre

Liver transplant seems to be an effective option to prolong survival in patients with end-stage liver disease, although it still can be followed by serious complications. Invasive fungal infections (ifi) are related to high rates of morbidity and mortality. The epidemiology of fungal infections in Brazilian liver transplant recipients is unknown. The aim of this observational and retrospective study was to determine the incidence and epidemiology of fungal infections in all patients who underwent liver transplantation at Albert Einstein Israeli Hospital between 2002-2007. A total of 596 liver transplants were performed in 540 patients. Overall, 77 fungal infections occurred in 68 (13%) patients. Among the 77 fungal infections, there were 40 IFI that occurred in 37 patients (7%). Candida and Aspergillus species were the most common etiologic agents. Candida species accounted for 82% of all fungal infections and for 67% of all IFI, while Aspergillus species accounted for 9% of all fungal infections and for 17% of all IFI. Non-albicans Candida species were the predominant Candida isolates. Invasive aspergillosis tended to occur earlier in the post-transplant period. These findings can contribute to improve antifungal prophylaxis and therapy practices in Brazilian centres.Universidade Federal de São Paulo (UNIFESP)Hospital Israelita Albert EinsteinUNIFESPSciEL

Intraspecific comparative genomics of Candida albicans mitochondria reveals non-coding regions under neutral evolution

The opportunistic fungal pathogen Candida albicans causes serious hematogenic hospital acquired candidiasis with worldwide impact on public health. Because of its importance as a nosocomial etiologic agent, C albicans genome has been largely studied to identify intraspecific variation and several typing methods have been developed to distinguish closely related strains. Mitochondrial DNA can be useful for this purpose because, as compared to nuclear DNA, its higher mutational load and evolutionary rate readily reveals microvariants. Accordingly, we sequenced and assembled, with 8-fold coverage, the mitochondria( genomes of two C albicans clinical isolates (L296 and L757) and compared these sequences with the genome sequence of reference strain SC5314. the genome alignment of 33,928 positions revealed 372 polymorphic sites being 230 in coding and 142 in non-coding regions. Three intergenic regions located between genes tRNAGly/COX1, NAD3/COB and ssurRNA/NAD4L, named IG1, IG2 and IG3, respectively, which showed high number of neutral substitutions, were amplified and sequenced from 18 clinical isolates from different locations in Latin America and 2 ATCC standard C albicans strains. High variability of sequence and size were observed, ranging up to 56 bp size difference and phylogenies based on IG1, IG2 and IG3 revealed three groups. Insertions of up to 49 bp were observed exclusively in Argentinean strains relative to the other sequences which could suggest clustering by geographical polymorphism. Because of neutral evolution, high variability, easy isolation by PCR and full length sequencing these mitochondrial intergenic regions can contribute with a novel perspective in molecular studies of C albicans isolates, complementing well established multilocus sequence typing methods. (C) 2012 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)International Program of the Howard Hughes Medical InstituteUniversidade Federal de São Paulo, Lab Genom Evolut & Biocomplexidade, Dept Microbiol Imunol & Parasitol, Disciplina Microbiol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Infectol, Lab Especial Micol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Lab Genom Evolut & Biocomplexidade, Dept Microbiol Imunol & Parasitol, Disciplina Microbiol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Infectol, Lab Especial Micol, BR-04039032 São Paulo, BrazilWeb of Scienc